A randomized, masked, controlled study of omega-3 polyunsaturated fatty acid vs monounsaturated fatty acid diet supplementation for the treatment of nonalcoholic fatty liver disease

Abstract

Background: Omega-3-polyunsaturated fatty acids have been shown to simultaneously suppress hepatic lipid synthesis while upregulating fatty acid oxidation in a mouse model of NASH. Numerous clinical studies using dietary supplementation with omega-3 polyunsaturated fatty acids (PUFA) have resulted in decreased VLDL cholesterol and serum trigylcerides. Aim: The aim of this study is to investigate the effects of an 8-week dietary supplementation with omega-3 polyunsaturated fatty acids (PUFA; i.e., fish oil) compared to monounsaturated fatty acids (MUFA; i.e., safflower oil) on intrahepatic fat content measured by magnetic resonance spectroscopy, serum aminotransferases, fasting lipids, insulin resistance, resting metabolic rate and proinflammatory cytokines in patients with non-alcoholic fatty liver disease. Methods: Fifteen subjects with NAFLD have enrolled in our study and underwent the following procedures at baseline and after 8-weeks of dietary supplementation with either fish oil or safflower oil: blood draw for liver tests, fasting lipids and inflammatory cytokines; oral glucose tolerance test; DEXA scan for body fat distribution; MRS for intrahepatic and abdominal visceral fat determination; indirect calorimetry for resting metabolic rates. Results: The following variables were associated with the amount of steatosis at baseline: total serum protein; ALT; AST/ALT; triglycerides; decreased HDL; triglyceride/HDL ratio; plasma insulin; c-peptide; HOMA-IR; and resting energy expenditure. There was no significant change in the degree of hepatic steatosis after therapy in either group (mean change PUFA group= +0.35%, p=0.57 vs mean change MUFA group= -0.61%, p=0.75; Wilcoxon signed-rank test). There was a significant increase in resting energy expenditure (1715 vs 1954 kcal/day, p=0.025; paired t test), improved insulin response (incremental AUC insulin/ incremental AUC glucose), (1.02 vs 1.27, p=0.025; paired t test) and total body fat mass (kg) determined by DEXA (30.5 kg vs 31.4 kg, p=0.032; paired t test) in the PUFA treated group following 8 weeks of therapy. There was a positive relationship between percent change in hepatic steatosis and percent change in glucose levels (R2=0.79, p=0.02) in the PUFA group. Conclusions: An 8 week course of omega-3 PUFA did not result in a significant decrease in the degree of hepatic steatosis as determined by MRS. However subjects in the PUFA group also had an increased body fat mass which may have contributed to their lack of decreased steatosis. PUFA therapy was associated with an improvement in resting metabolic rate and insulin response. Further studies are needed to the mechanism for this.